[Clinical study of the cytokine panel in the diagnosis of ocular chronic graft-versus-host disease].

Objective: To investigate the association between cytokines and ocular chronic graft-versus-host disease (cGVHD) and identify specific biomarkers for ocular cGVHD to enhance clinical diagnosis, treatment, and evaluation. Methods: A mouse model of cGVHD was established to explore the correlation between cGVHD and serum cytokines. Based on the findings from the animal experiments and literature review, a panel of 16 cytokine combinations was identified. Enzyme-linked immunosorbent assay (ELISA) was used to compare the cytokine concentrations in the serum and tear samples from patients who underwent allogeneic hematopoietic stem cell transplantation from June 2017 to March 2022 at the Medical Center of Hematology, Xinqiao Hospital, Army Medical University. Results: ① Compared with the control group, mice with cGVHD exhibited elevated serum IL-1ß, IL-6, IL-8, IL-17, IFN-γ, CX3CL1, CXCL11, CXCL13, CCL11, and CCL19 concentrations (all P<0.05). ② Analysis of the cytokine profiles of the serum and tear samples revealed that compared with patients without ocular cGVHD, those with ocular cGVHD exhibited increased serum IL-8 [P=0.032, area under the curve (AUC) =0.678]; decreased serum IL-10 (P=0.030, AUC=0.701) ; elevated IL-8, IFN-γ, CXCL9, and CCL17 in tear samples; and lower IL-10 and CCL19 in tear samples (all P<0.05, all AUC>0.7). Moreover, cytokines in tear samples showed correlations with ocular surface parameters related to ocular cGVHD. Conclusions: Tear fluid demonstrates greater specificity and sensitivity as a biomarker for diagnosing ocular cGVHD than serum biomarkers. Among the identified cytokines in tear samples, IL-8, IL-10, IFN-γ, CXCL9, CCL17, and CCL19 serve as diagnostic biomarkers for ocular cGVHD post-transplantation, offering practical reference value for diagnosis.

[Evaluation of differences in quality of life in patients with chronic graft-versus-host disease].

Objective: To evaluate the status of, differences in, and factors influencing quality of life (QoL) in patients with chronic graft-versus-host disease (GVHD). Methods: From September 2021 to February 2023, a cross-sectional study of 140 patients with chronic GVHD was conducted at our center. Symptom burden was assessed by the Lee Symptomatology Scale (LSS), and QoL was assessed by the Medical Outcome Study 36-Item Short-Form Health Survey (SF-36) (version 1) and five-level EuroQoL five-dimensional questionnaire (EQ-5D-5L). Results: Data from 140 respondents, including 32 (22.9%) with mild chronic GVHD, 87 (62.1%) with moderate chronic GVHD, and 21 (15.0%) with severe chronic GVHD, were analyzed. Of the respondents, 61.4% were male, and the median transplantation age was 34 (15-68) years. The primary diagnoses were acute myeloid leukemia (50.0%), acute lymphoblastic leukemia (20.0%), and myelodysplastic syndrome (15.0%). The common chronic GVHD-affected organs included the skin in 74 patients (52.9%), the eyes in 57 patients (40.7%), and the liver in 50 patients (35.7%). Among the whole cohort, the eye (20.48±23.75), psychological (16.13±17.00), and oral (13.66±20.55) scores were highest in the LSS group. The physiological function (36.07±11.13), social function (36.10±10.68), and role-emotional functioning (38.36±11.88) scores were lowest in the SF-36 group. The EQ-5D index was 0.764. The total LSS scores for mild, moderate, and severe chronic GVHD were 6.51±6.15, 10.07±5.61, and 20.90±10.09, respectively. The SF-36 physical component scores (PCSs) were 43.12±6.38, 40.73±7.14, and 36.97±6.97, respectively, and the mental component scores (MCSs) were 43.00±8.47, 38.90±9.52, and 28.96±9.63, respectively. The EQ-5D values were 0.810±0.124, 0.762±0.179, and 0.702±0.198, respectively. The multivariate analysis showed that the overall symptom burden (ß=-0.517), oral symptom burden (ß=-0.456), National Institute of Health (NIH) criteria for the eyes (ß=-0.376), and nutrition-related symptom burden (ß=-0.211) were significantly negatively correlated with the PCS. The NIH score (ß=-0.260) was negatively correlated with the MCS score. Oral symptom burden (ß=-0.400), joint/fascia NIH criteria (ß=-0.332), number of involved systems (ß=-0.253), overall NIH criteria (ß=-0.205), and number of immunosuppressants taken (ß=-0.171) were significantly negatively correlated with the EQ-5D score (all P<0.05). Medium to strong correlations were found between the EQ-5D score and the SF-36 score (|r|=0.384-0.571, P<0.001). Conclusions: The QoL of patients with chronic GVHD is impaired, and the more severe the disease, the poorer the QoL. Overall symptom burden, severity of eyes, and oral symptom burden were the most important factors affecting QoL.

[Disease burden of acute viral hepatitis in Guangdong Province, 1990-2019].

Objective: To examine the burden and trends of acute viral hepatitis in Guangdong Province from 1990 to 2019, and provide reference evidences for hepatitis prevention and control in the province. Methods: Data on acute viral hepatitis (hepatitis A, B, C, and E) in Guangdong from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database. The incidence, prevalence, mortality, and disability-adjusted life years (DALY) data were analyzed by age and gender, and the estimated annual percentage change (EAPC) was calculated to describe the changing trends in disease burden. Results: From 1999 to 2019, the standardized incidence, prevalence, mortality, and DALY of acute viral hepatitis in Guangdong were higher than the national averages. In 2019, 51.43% (2 245 087/4 365 221) of acute viral hepatitis cases in Guangdong Province were mainly attributed to hepatitis B, and 77.18% (106/138) of deaths were due to acute hepatitis B. In different age groups, except for acute hepatitis B, which was more common in adults, the incidence rates of other types of viral hepatitis such as hepatitis A, B, and E showed an overall decreasing trend with age. The mortality rates of different types of acute viral hepatitis, except for the <5 age group, increased with age. The overall incidence and mortality rates of acute viral hepatitis were higher in men than in women. Conclusions: The overall burden of acute viral hepatitis in Guangdong declined in 2019, but remained higher than the national level. Further efforts are needed to strengthen hepatitis prevention and screening in different population in Guangdong Province, especially in children and the elderly.

Ultrasonic bone curette in thoracic spinal decompression: a comprehensive systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to compare the efficacy and safety of ultrasonic bone curette (UBC) and conventional surgical instruments in thoracic laminectomy decompression (TLD) for the treatment of thoracic spinal stenosis (TSS) by meta-analysis. MATERIALS AND METHODS: Two authors independently searched Medline via PubMed, Embase, Cochrane Library, Web of Science, Wanfang Database, and China National Knowledge Infrastructure for the period from the establishment of the database until January 2023 to identify the studies on the safety and efficacy of UBC vs. conventional instruments for TSS. Data extraction and quality assessment were performed by two researchers independently. We used RevMan 5.4 software (Review Manager Web, The Cochrane Collaboration, Copenhagen, Denmark) to analyze the data. RESULTS: Eight retrospective studies were included in the present work. This meta-analysis revealed that no significant differences in the preoperative JOA scores, the JOA scores at the last follow-up, the improvement rate of JOA scores, and the incidence of cerebrospinal fluid leakage/dura injury were detected between the two groups (p>0.05). However, there were significant differences in the operative time and intraoperative blood loss during single-level TLD [operative time: MD=-1.47, 95% CI (-1.86, -1.09), p<0.001; intraoperative blood loss: MD=-46.62, 95% CI (-53.83, -39.40), p<0.001], total operative time [MD=-56.88, 95% CI (-69.66, -44.10), p<0.001], total intraoperative blood loss [MD=-143.52, 95% CI (-212.49, -74.54), p<0.001], the incidence of neurological deterioration/nerve root injury [RR= 0.29, 95% CI (0.09, 0.91), p=0.03] between the groups. CONCLUSIONS: The application of UBC in TLD to treat TSS is safe and effective. UBC can significantly shorten operation time and reduce intraoperative blood loss compared to traditional surgical instruments. Moreover, it has the advantage of reducing perioperative nerve injury.

Metformin reduces decline in the estimated glomerular filtration rate during progression of autosomal dominant polycystic kidney disease: a systematic review and meta-analysis.

OBJECTIVE: A meta-analysis (MA) was carried out to examine the influence of metformin on autosomal dominant polycystic kidney disease (ADPKD) patient prognosis. MATERIALS AND METHODS: We reviewed and examined scientific articles from PubMed, Clinicalkey, Google Scholar, Medline, Embase, and Cochrane from the initiation date till June 2023 to identify investigations that examined metformin performance in managing ADPKD. Among the employed search terminology, we searched for terms such as "metformin" and "ADPKD". MA was conducted using the Cochrane Collaboration's RevMan version 5.3.0 (The Cochrane Collaboration, Oxford, UK). RESULTS: We identified 4 investigations, with 164 total subjects who fulfilled our inclusion criteria. The experimental cohort displayed a marked reduction in the decline of estimated glomerular filtration rate (eGFR) relative to controls [mean difference (MD) = 2.31, 95% confidence interval (CI) = 0.82-3.79, p = 0.002]. We observed no obvious difference in the height-adjusted total kidney volume alteration, gastrointestinal side effects, and hypoglycemia between the two cohorts. CONCLUSIONS: Metformin was easily tolerable and safe and substantially reduced the eGFR decline among ADPKD patients. Moreover, although metformin-treated patients were more likely to suffer gastrointestinal adverse events, we observed no discernible difference between the two cohorts.

Analyses of microRNA166 gene structure, expression, and function during the early stage of somatic embryogenesis in Dimocarpus longan Lour.

MicroRNA166 (miR166) contributes to post-transcriptional regulation by binding the mRNAs of HD-ZIP III genes, which affects plant growth and development. The structural characteristics, expression, and functions of miR166 genes during the early somatic embryogenesis stage in Dimocarpus longan remain unknown. We isolated the transcripts of pri-miR166 S78 with two transcription initiation sites (TSSs) and pri-miR166 S338 with one TSS. These sequences contain potential smORFs and encode different miRNA peptides (miPEPs). Additionally, their promoters contain cis-acting elements responsive to diverse stimuli. The pre-miR166 S78 and pre-miR166 S338 expression levels were up-regulated in response to 2,4-D, abscisic acid, and ethylene. Although the expression patterns induced by hormones were similar, there were differences in the extent of the response, with pre-miR166 S338 more responsive than pre-miR166 S78. Thus, miRNA transcription and maturation are not simply linearly correlated. Moreover, pre-miR166 S78 and pre-miR166 S338 expression levels were down-regulated, whereas ATHB15 (target gene) expression was up-regulated, from the longan embryonic callus to the globular embryo stages. These results are indicative of a negative regulatory relationship between miR166 and ATHB15 during the early somatic embryogenesis stage in longan. At the same stages, miR166a.2-agomir, miR166a.2-antagomir, and miPEP166 S338 increased or decreased the expression of miR166a.2 and ATHB15, but with no consistent patterns or linear synchronization, from which we've found some reasons for it.

Nectar yeasts enhance the interaction between Clematis akebioides and its bumblebee pollinator.

It has been hypothesised that intense metabolism of nectar-inhabiting yeasts (NIY) may change nectar chemistry, including volatile profile, which may affect pollinator foraging behaviours and consequently plant fitness. However, empirical evidence for the plant-microbe-pollinator interactions remains little known. To test this hypothesis, we use a bumblebee-pollinated vine Clematis akebioides endemic to southwest China as an experimental model plant. To quantify the incidence and density of Metschnikowia reukaufii, a cosmopolitan NIY in floral nectar, a combination of yeast cultivation and microscopic cell-counting method was used. To examine the effects of NIY on plant-pollinator interactions, we used real flowers filled with artificial nectar with or without yeast cells. Then the volatile metabolites produced in the yeast-inoculated nectar were analysed with coupled gas chromatography and mass spectrometry (GC-MS). On average 79.3% of the C. akebioides flowers harboured M. reukaufii, and cell density of NIY was high to 7.4 × 104 cells mm-3 . In the field population, the presence of NIY in flowers of C. akebioides increased bumblebee (Bombus friseanus) pollinator visitation rate and consequently seed set per flower. A variety of fatty acid derivatives produced by M. reukaufii may be responsible for the above beneficial interactions. The volatiles produced by the metabolism of M. reukaufii may serve as an honest signal to attract bumblebee pollinators and indirectly promote the female reproductive fitness of C. akebioides, forming a potentially tripartite plant-microbe-pollinator mutualism.

Tyrosine kinase Pyk2 is involved in colonic smooth muscle contraction via the RhoA/ROCK pathway.

The contraction of gastrointestinal (GI) smooth muscles is regulated by both Ca(2+)-dependent and Ca(2+) sensitization mechanisms. Proline-rich tyrosine kinase 2 (Pyk2) is involved in the depolarization-induced contraction of vascular smooth muscle via a Ca(2+) sensitization pathway. However, the role of Pyk2 in GI smooth muscle contraction is unclear. The spontaneous contraction of colonic smooth muscle was measured by using isometric force transducers. Protein and phosphorylation levels were determined by using western blotting. Pyk2 protein was expressed in colonic tissue, and spontaneous colonic contractions were inhibited by PF-431396, a Pyk2 inhibitor, in the presence of tetrodotoxin (TTX). In cultured colonic smooth muscle cells (CSMCs), PF-431396 decreased the levels of myosin light chain (MLC20) phosphorylated at Ser19 and ROCK2 protein expression, but myosin light chain kinase (MLCK) expression was not altered. However, Y-27632, a Rho kinase inhibitor, increased phosphorylation of Pyk2 at Tyr402 and concomitantly decreased ROCK2 levels; the expression of MLCK in CSMCs did not change. The expression of P(Tyr402)-Pyk2 and ROCK2 was increased when CSMCs were treated with Ach. Pyk2 is involved in the process of colonic smooth muscle contraction through the RhoA/ROCK pathway. These pathways may provide very important targets for investigating GI motility disorders.

Pituitary tumor transforming gene binding factor (PBF) is required for androgen-induced prostate cancer proliferation and invasion.

Pituitary tumor transforming gene binding factor (PBF) is a proto-oncogene that plays a role in many cancers; however, its involvement in prostate cancer (PCa) remains unclear. Here, we examined PBF expression in clinical specimens and investigated its regulation and function in human PCa cell lines. Immunohistochemical staining of patient tissues revealed higher PBF expression in PCa than in benign prostatic hyperplasia or adjacent normal prostate specimens. In LNCaP and 22Rv1 cells, PBF expression was upregulated by androgen treatment in a manner partially blocked by the androgen receptor (AR) antagonist bicalutamide. We identified a novel androgen response element in the PBF gene promoter and demonstrated its functional relevance using luciferase reporter assays. Androgen treatment of LNCaP cells induced binding between the endogenous AR and the androgen response element in PBF, as measured by chromatin immunoprecipitation assays. Finally, RNA interference of PBF expression significantly reduced androgen-induced LNCaP cell growth and invasion. Thus, PBF is a novel AR target gene and plays a role in androgen-induced proliferation and metastatic functions in PCa cells.

Long non-coding RNA expression profile in permanent atrial fibrillation patients with rheumatic heart disease.

OBJECTIVE: Atrial fibrillation (AF) is the most common type of arrhythmia, especially in rheumatic heart disease (RHD) patients. The differences in structural remodeling and electrical remodeling between the left and right atrium associated with AF in RHD patients are well known, and alterations in the expression profiles of long noncoding RNAs (lncRNAs) in the left atrium have also been investigated. However, the role of lncRNAs in the right atrium (RA) remains largely unknown. PATIENTS AND METHODS: We identified differentially expressed lncRNAs in RA tissues of RHD patients with AF or a normal sinus rhythm (NSR) using microarray analysis. Then, we performed gene ontology (GO) and KEGG pathway analyses for functional annotation of the deregulated lncRNAs. Finally, we constructed a lncRNA-mRNA co-expression network. RESULTS: Of the 22,829 human non-coding RNAs analyzed, a total of 1,909 long non-coding RNAs were detected. A total of 182 lncRNAs (117 downregulated and 65 upregulated) were shown to be differentially expressed (fold-change > 1.5) in AF patients compared with NSR patients. Many lncRNAs might be partially involved in an AF-related pathway. CONCLUSIONS: AF dysregulates the expression of lncRNAs in the RA of RHD patients. These findings may be useful for exploring potential therapeutic treatments for AF in RHD patients.

Diabetes-induced colonic slow transit mediated by the up-regulation of PDGFRα+ cells/SK3 in streptozotocin-induced diabetic mice.

BACKGROUND: A major complication related to gastrointestinal (GI) symptoms in diabetic patients is chronic constipation. Constipation has serious negative impacts on quality of life; however, without a comprehensive understanding of the disease, currently available treatments cannot provide a cure. Platelet-derived growth factor receptor alpha-positive cells (PDGFRα+ cells), which form the SIP syncytium with interstitial cells of Cajal and smooth muscle cells, play important roles in GI motility. In the present study, the contributions of PDGFRα+ cells to diabetes-induced colonic slow transit were investigated in streptozotocin (STZ)-induced diabetic mice. METHODS: Western blotting, quantitative PCR, contractile experiments, and intracellular recording were used in the present study. KEY RESULTS: The results demonstrated that the colon length was increased in STZ-treated mice. The colonic transit of artificial fecal pellets in vitro was significantly delayed in STZ-treated mice. The mRNA and protein expression of PDGFRα, small-conductance Ca2+ -activated K channels (SK3), and P2Y1 receptors were increased in the colons of STZ-treated mice. In contractile experiments, the colonic smooth muscles were more sensitive to the SK3 agonist and antagonist (CyPPA and apamin) and the P2Y1 agonist and antagonist (MRS2365 and MRS2500) in STZ-treated mice. Intracellular recordings showed the responses of membrane potentials in colonic smooth muscle cells to CyPPA, apamin, MRS2365, and MRS2500 were more sensitive in STZ-treated mice. The electric field stimulation-induced P2Y1/SK3-dependent fast inhibitory junctional potentials (fIJPs) of colonic smooth muscles were more significantly hyperpolarized in STZ-treated mice. CONCLUSIONS AND INFERENCES: These results suggest that the purinergic neurotransmitters/P2Y1/SK3 signaling pathway is up-regulated in the diabetic colons, thereby mediating diabetes-induced colonic slow transit.

Geometric Parameter Analysis of Ruptured and Unruptured Aneurysms in Patients with Symmetric Bilateral Intracranial Aneurysms: A Multicenter CT Angiography Study.

BACKGROUND AND PURPOSE: Previous studies of geometric and morphologic parameters of intracranial aneurysms have been conducted to determine rupture risk, which remains incompletely defined due to patient-specific risk factors, such as sex, hypertension, and age. To this end, we compared characteristics of ruptured and unruptured aneurysms in the same patients with symmetric bilateral intracranial aneurysms. MATERIALS AND METHODS: Between January 2008 and March 2014, 2361 patients with 2674 aneurysms were diagnosed by CT angiography or surgical findings at 4 medical centers. Geometric and morphologic parameters examined for symmetric bilateral intracranial aneurysms comprised aneurysm wall regularity, size, neck width, aspect ratio, size ratio, neck-to-parent artery ratio, and area ratio. Univariate and multivariate statistical analyses were performed to determine independent risk factors for rupture. RESULTS: Sixty-three patients (48 women, 15 men; mean age, 62.5 ± 9.8 years) with symmetric bilateral aneurysms were eligible for the study and were included. The most frequent aneurysm location was the posterior communicating artery. Univariate analysis disclosed that aneurysm size, aspect ratio, size ratio, area ratio, and irregular wall differed between patients with ruptured and unruptured aneurysms. Multivariate analysis indicated that aspect ratio of ≥1.6 (adjusted OR, 9.521; 95% CI, 2.182-41.535), area ratio of ≥1.5 (adjusted OR, 4.089; 95% CI, 1.247-13.406), and irregular shape (adjusted OR, 10.443; 95% CI 3.394-32.135) were significant predictive factors for aneurysm rupture after adjustment for aneurysm size. CONCLUSIONS: An aspect ratio of ≥1.6, area ratio of ≥1.5, and irregular wall are associated with aneurysm rupture independent of aneurysm size and patient characteristics. These characteristics alone can help in distinguishing ruptured bilateral intracranial aneurysms from unruptured ones.

Role of pleth variability index for predicting hypotension after spinal anesthesia for cesarean section.

BACKGROUND: Hypotension is frequently observed after spinal anesthesia for cesarean section and can be detrimental to both mother and baby. We investigated the role of the pleth variability index for predicting hypotension after spinal anesthesia for cesarean section. METHODS: Eighty-five parturients undergoing elective cesarean section under spinal anesthesia were enrolled. We recorded pleth variability index and perfusion index before anesthesia, and blood pressure, heart rate and pulse oxygen saturation before and after anesthesia. The association between baseline pleth variability index and perfusion index with hypotension after spinal anesthesia was explored using multivariate analysis. RESULTS: Hypotension occurred in 42 parturients. Baseline pleth variability index was higher in parturients who experienced hypotension than in those who did not (P<0.05), although there was no difference in baseline perfusion index. The area under the receiver operating characteristic curve was 0.66 for baseline pleth variability index for the prediction of hypotension (P<0.05). Baseline pleth variability index was significantly related to the incidence of hypotension (P=0.017), but was not significantly related to the magnitude of the decrease in systolic blood pressure. Baseline perfusion index was not significantly related to the magnitude of the decrease in systolic blood pressure. CONCLUSION: Greater baseline pleth variability index was associated with hypotension after spinal anesthesia for cesarean section, but may not be a clinically useful predictor.

Interspecific variation in pollen-ovule ratio is negatively correlated with pollen transfer efficiency in a natural community.

The pollination efficiency hypothesis has long been proposed as an explanation for interspecific variation in pollen-ovule (P:O) ratios. However, no empirical study on P:O ratios has directly and quantitatively measured pollen transfer efficiency (PE). Here, we use a PE index, defined as the proportion of pollen grains removed from anthers that are subsequently deposited on conspecific stigmas, as a direct and quantitative measure of PE. We investigated P:O ratios, pollen removal and pollen deposition in 26 plant species in an alpine meadow, over three consecutive years. Our community survey showed that nearly 5% of removed pollen was successfully deposited on conspecific stigmas. The PE index ranged from 0.01% up to 78.56% among species, and correlated negatively with the P:O ratio across years. This correlation was not changed by controlling for phylogenetic relationships among species, suggesting that the interspecific variation in P:O ratios can be attributed to the probability of pollen grains reaching a stigma. The results indicate that the pollination efficiency hypothesis can help to explain interspecific variation in P:O ratios.

Epsilon-aminocaproic acid improves postrecirculation hemodynamics by reducing intraliver activated protein C consumption in orthotopic liver transplantation.

BACKGROUND: Activated protein C (APC) is related to regulating the inflammatory response and hemodynamic stability upon reperfusion in cardiac operations and orthotopic liver transplantation (OLT). Epsilon-aminocaproic acid (EACA) is frequently used to treat fibrinolysis during OLT. It also has inhibitory effects related to the inflammatory response. However, it remains to be determined whether EACA can attenuate intraliver APC consumption and improve hemodynamic stability after reperfusion during OLT. METHODS: Fifty-nine recipients were randomized to receive either EACA (150 mg kg(-1) given intravenously prior to incision, followed by 15 mg kg(-1) h(-1) infusion until 2 h after the graft reperfusion) or the same volume of saline. Blood samples to assess plasma APC and protein C were obtained immediately before and after reperfusion from the inferior caval effluent or the portal veins for calculation of transliver differences (Δ). Hemodynamics and vasoactive medication use during the reperfusion period were observed in both groups. RESULTS: No transhepatic changes in protein C were found in either group. Immediately after reperfusion, a marked intraliver consumption of APC was noted in all recipients (P < 0.001), and intraliver consumption of APC in the control group was greater than that in the EACA-treated group (P < 0.05). Fewer requirements for vasoactive medication use after reperfusion and better initial graft function were noted in the EACA-treated group (P < 0.05). CONCLUSIONS: EACA can attenuate intraliver APC consumption and improve hemodynamic stability after reperfusion and initial graft function during OLT.

Novel cerebellum-enriched miR-592 may play a role in neural progenitor cell differentiation and neuronal maturation through regulating Lrrc4c and Nfasc in rat.

MicroRNAs (miRNAs) are a class of small non-encoding RNAs that regulate gene expression at the posttranscriptional level. MiRNAs may characterize not only specific stages of the development of the neural cell population in CNS, but also distinct types of neural cells. However, the common pathways of the neural enriched miRNAs involved in neurogenesis of specific cell lineages remain poorly understood. In this report, in order to get insights into the common role of the miRNAs shared by cerebellum and forebrain, we studied the regulatory mechanism of neural enriched-miRNA in neural progenitor cell (NPCs) differentiation. Here, we identified a new cerebellum-enriched rno-miR-592 in rat cerebellum. It showed that rno-miR-592 was a neural enriched miRNA and may play an important role in rat embryonic neurogenesis or/and astrogliogenesis. We used both gain-of -function and loss-of -function approaches to demonstrate that rno-miR-592 could change the balance between neuron- and astrocyte- like differentiation and neuronal morphology. We observed that miR-592 could induce astrogliogenesis differentiation arrest or/and enhance neurogenesis in vitro. Meanwhile, silencing of miR-592 was not beneficial for neuronal maturation. We also identified Lrrc4c and Nfasc as miR-592 target genes, and miR-592 could affect the changes of Lrrc4c and Nfasc expression levels, suggesting that these two target genes may be involved in miR-592 regulative function in NPCs differentiation and neuronal maturation. Thus, we conclude that rno-miR-592 may affect the neural lineage differentiation via reducing astrogliogenesis or/and enhancing neurogenesis at least in part through regulating its target genes Lrrc4c and Nfasc in vitro. Together, we report here for the first time the important role of miR-592 in rat NPCs differentiation and neuronal maturation.

Role of anhepatic time in endothelial-related coagulation in liver transplantation.

BACKGROUND: Disturbances in coagulation homeostasis are common in patients undergoing orthotopic liver transplantation (OLT) and anhepatic period is one of the important factors related to the coagulation abnormalities. The endothelium can regulate hemostasisby producing substances such as thrombomodulin (TM). The primary aim was to evaluate the effect of an hepatic time on the thrombomodulin-protein C system in patients undergoing OLT. METHODS: Fifty patients undergoing OLT were stratified in two groups: anhepatic time ≥ 60 min (N.=18) or anhepatic stage <60 min (N.=32). TM, protein C, activated protein C (APC) and (free) protein S plasma concentrations were measured by enzymelinked immunosorbent assays (ELISA) at the start of the surgery (To); immediately before the anhepatic period (A1); immediately before reperfusion (A2); 5 minutes; 15 minutes; 30 minutes after reperfusion of the graft (R1; R2; R3); at the end of operation (R4); the first day after operation (R5). RESULTS: Blood loss and transfusion were significantly greater in patients whose anhepatic time ≥ 60 min during the operation. TM levels increased most in patients whose anhepatic time ≥ 60 min. Protein C levels remained low throughout the surgery and decreased significantly at other points compared with To (P<0.05). There were no differences in protein C levels between groups except R5. The ratio of circulating APC activity to protein C antigen (APC/PC) increased significantly during the surgery. APC/PC ratio in the neohepatic stage increased significantly in patients whose anhepatic time ≥ 60 min (P<0.05). CONCLUSION: Patients with prolonged anhepatic time had greater changes in the thrombomodulin-protein C system.

An MPS-BNS mixed strategy based on game theory for wireless mesh networks.

To achieve a valid effect of wireless mesh networks against selfish nodes and selfish behaviors in the packets forwarding, an approach named mixed MPS-BNS strategy is proposed in this paper. The proposed strategy is based on the Maximum Payoff Strategy (MPS) and the Best Neighbor Strategy (BNS). In this strategy, every node plays a packet forwarding game with its neighbors and records the total payoff of the game. After one round of play, each player chooses the MPS or BNS strategy for certain probabilities and updates the strategy accordingly. In MPS strategy, each node chooses a strategy that will get the maximum payoff according to its neighbor's strategy. In BNS strategy, each node follows the strategy of its neighbor with the maximum total payoff and then enters the next round of play. The simulation analysis has shown that MPS-BNS strategy is able to evolve to the maximum expected level of average payoff with faster speed than the pure BNS strategy, especially in the packets forwarding beginning with a low cooperation level. It is concluded that MPS-BNS strategy is effective in fighting against selfishness in different levels and can achieve a preferable performance.

RNAi-mediated knockdown of pituitary tumor- transforming gene-1 (PTTG1) suppresses the proliferation and invasive potential of PC3 human prostate cancer cells

Pituitary tumor-transforming gene-1 (PTTG1) is a proto-oncogene that promotes tumorigenesis and metastasis in numerous cell types and is overexpressed in a variety of human tumors. We have demonstrated that PTTG1 expression was up-regulated in both human prostate cancer specimens and prostate cancer cell lines. For a more direct assessment of the function of PTTG1 in prostate tumorigenesis, RNAi-mediated knockdown was used to selectively decrease PTTG1 expression in PC3 human prostate tumor cells. After three weeks of selection, colonies stably transfected with PTTG1-targeted RNAi (the knockdown PC3 cell line) or empty vector (the control PC3 cell line) were selected and expanded to investigate the role of PTTG1 expression in PC3 cell growth and invasion. Cell proliferation rate was significantly slower (28%) in the PTTG1 knockdown line after 6 days of growth as indicated by an MTT cell viability assay (P < 0.05). Similarly, a soft agar colony formation assay revealed significantly fewer (66.7%) PTTG1 knockdown PC3 cell colonies than control colonies after three weeks of growth. In addition, PTTG1 knockdown resulted in cell cycle arrest at G1 as indicated by fluorescence-activated cell sorting. The PTTG1 knockdown PC3 cell line also exhibited significantly reduced migration through Matrigel in a transwell assay of invasive potential, and down-regulation of PTTG1 could lead to increased sensitivity of these prostate cancer cells to a commonly used anticancer drug, taxol. Thus, PTTG1 expression is crucial for PC3 cell proliferation and invasion, and could be a promising new target for prostate cancer therapy.